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A prosthesis can be configured to grasp intralumenal tissue when deployed within a body cavity and prevent axial flow of fluid around an exterior of the prosthesis. The prosthesis can include an expandable frame configured to radially expand and contract for deployment within the body cavity, and an

A prosthesis can be configured to grasp intralumenal tissue when deployed within a body cavity and prevent axial flow of fluid around an exterior of the prosthesis. The prosthesis can include an expandable frame configured to radially expand and contract for deployment within the body cavity, and an outer skirt positioned annularly around an exterior of the expandable frame. In some embodiments, the outer skirt can extend outward from the frame and be secured to an outwardly extending anchor on the frame to create an axial barrier to fluid flow exterior to the frame when deployed within the body cavity.

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1. A prosthesis configured to grasp intralumenal tissue when deployed within a body cavity and prevent axial flow of fluid around an exterior of the prosthesis, the prosthesis comprising: an expandable frame comprising a proximal end and a distal end and a longitudinal axis extending therethrough, t

1. A prosthesis configured to grasp intralumenal tissue when deployed within a body cavity and prevent axial flow of fluid around an exterior of the prosthesis, the prosthesis comprising: an expandable frame comprising a proximal end and a distal end and a longitudinal axis extending therethrough, the frame configured to radially expand and contract for deployment within the body cavity;a plurality of anchors each connected to the frame so that when the frame is in an expanded configuration an end of each anchor is positioned radially outward from the frame, the plurality of anchors comprising a plurality of distal anchors having ends which extend proximally when the frame is in an expanded configuration, the ends of the distal anchors being circumferentially spaced apart such that at least one of the plurality of distal anchors is configured to extend between chordae tendineae when the frame is in an expanded configuration; anda skirt annularly positioned around an exterior of the expandable frame to create an axial barrier to fluid flow exterior to the frame when deployed within the body cavity, the skirt comprising: a first portion having a proximal end and a distal end, the proximal end being positioned at a location spaced between the proximal and distal ends of the frame and being unattached to the frame or plurality of anchors, the distal end of the first portion being positioned closer to the distal end of the frame than the proximal end of the first portion; anda second portion shaped to extend radially outward from the frame at a location spaced between the proximal end and the distal end to prevent axial flow of fluid around an exterior of the prosthesis, the second portion shaped to extend radially from a proximal end of the first portion;wherein when the frame is in an expanded configuration, the frame has a larger cross-sectional dimension in a middle portion of the frame and a smaller cross-sectional dimension in a proximal portion and a distal portion of the frame, and wherein the ends of the anchors are positioned radially outward from the middle portion of the frame. 2. The prosthesis of claim 1, wherein the skirt comprises a plurality of wings or sleeves that surround at least some of the anchors. 3. The prosthesis of claim 1, wherein at least some of the plurality of anchors comprise looped ends, and the skirt is attached to the looped ends. 4. The prosthesis of claim 1, wherein the plurality of anchors comprise a plurality of proximal anchors having ends which extend distally when the frame is in an expanded configuration, wherein the ends of the proximal anchors are axially spaced from the ends of the distal anchors when the frame is in an expanded configuration. 5. The prosthesis of claim 4, wherein the skirt is secured to at least some of the proximal anchors. 6. The prosthesis of claim 5, wherein the skirt extends distally from the ends of the proximal anchors to a free distal edge. 7. The prosthesis of claim 4, wherein the second portion of the skirt is configured to extend radially outward from the frame between ends of the proximal and distal anchors. 8. The prosthesis of claim 4, wherein the plurality of proximal anchors are integrally formed with the frame. 9. The prosthesis of claim 1, further comprising a second skirt covering distal anchors to facilitate in-growth of adjacent tissue when the prosthesis is deployed within a body cavity. 10. The prosthesis of claim 1, further comprising a valve body attached to the frame. 11. The prosthesis of claim 1, wherein the proximal end and the distal end have substantially the same cross-sectional dimension. 12. A replacement heart valve suitable for use for securement to a native mitral valve annulus, comprising the prosthesis of claim 1. 13. The prosthesis of claim 12, wherein the middle portion of the frame is configured to engage tissue of a native mitral valve. 14. The prosthesis of claim 1, wherein the second portion of the skirt is configured to extend radially outward from the middle portion of the frame. 15. The prosthesis of claim 1, wherein the first portion of the skirt is configured to surround a middle portion of the frame, the middle portion of the frame being configured to engage intalumenal tissue. 16. A prosthesis configured to grasp intralumenal tissue when deployed within a body cavity and prevent axial flow of fluid around in exterior of the prosthesis, the prosthesis comprising: an expandable frame comprising a proximal end and a distal end and a longitudinal axis extending therethrough, the frame configured to radially expand and contract for deployment within the body cavity;a distal anchoring portion connected to the frame so that when the frame is in an expanded configuration an end of the distal anchoring portion is positioned radially outward from the frame, the distal anchoring portion comprising a plurality of distal anchors comprising circumferentially spaced apart ends; anda skirt annularly positioned around an exterior of the expandable frame to create an axial barrier to fluid flow exterior to the frame when deployed within the body cavity, the axial barrier being positioned at least proximally of the end of the distal anchoring portion, the skirt comprising: a first portion having a proximal end and a distal end, the distal end of the first portion being positioned more distal than the end of the distal anchoring portion; anda second portion shaped to extend radially outward from the frame at a location spaced between the proximal end and the distal end to prevent axial flow of fluid around an exterior of the prosthesis;wherein when the frame is in an expanded configuration: a cross-sectional dimension of the proximal end of the frame;the distal end of the frame and the proximal end have different cross-sectional dimensions, andthe ends of the anchors are positioned radially outward from the middle portion of the frame. 17. The prosthesis of claim 16, the prosthesis comprising a proximal anchoring portion connected to the frame so that when the frame is in an expanded configuration an end of the proximal anchoring portion is positioned radially outward from the frame. 18. The prosthesis of claim 17, wherein the proximal anchoring portion comprises a plurality of proximal anchors and wherein the plurality of proximal anchors and the plurality of distal anchors are circumferentially staggered. 19. The prosthesis of claim 16, wherein at least some of the plurality of distal anchors are sized to extend between at least some of the chordae tendineae. 20. The prosthesis of claim 16, wherein the distal end of the first portion is positioned at a base of the distal anchoring portion. 21. The prosthesis of claim 16, wherein the distal anchoring portion comprises at least six distal anchors. 22. A prosthesis configured to grasp intralumenal tissue when deployed within a native mitral valve and prevent axial flow of fluid around in exterior of the prosthesis, the prosthesis comprising: an expandable frame comprising a proximal end and a distal end and a longitudinal axis extending therethrough, the frame configured to radially expand and contract for deployment within the native mitral valve;a proximal anchoring portion sized to contact an atrial side of a native mitral valve annulus when the prosthesis is deployed within the native mitral valve, the proximal anchoring portion being connected to the frame at a location distal of the proximal end of the frame, wherein the proximal anchoring portion extends radially outward from the frame when the frame is in an expanded configuration;a distal anchoring portion sized to be positioned on a ventricular side of the native mitral valve annulus when the prosthesis is deployed within the native mitral valve, the distal anchoring portion comprising a plurality of spaced apart distal anchors extending towards a proximal end of the expandable frame, wherein the distal anchors are positioned radially outward from the frame when the frame is in an expanded configuration; anda skirt disposed along an exterior of the prosthesis to create an axial barrier to fluid flow exterior to the prosthesis when deployed within the native mitral valve, the skirt comprising: a generally cylindrical portion extending along an exterior of the frame, wherein a proximal end of the generally cylindrical portion is positioned distally of the proximal end of the frame and a distal end of the generally cylindrical portion is positioned proximally of the distal anchors; anda ring portion sized to contact an atrial side of a native mitral valve annulus when the prosthesis is expanded and deployed within the native mitral valve, the ring portion extending radially outward from the frame at the proximal end of the generally cylindrical portion, wherein at least a portion of the ring portion extends along the proximal anchoring portion;wherein when the frame is in an expanded configuration a cross-sectional dimension in a middle portion of the frame is larger than a cross-sectional dimension of the proximal end of the frame. 23. The prosthesis of claim 22, wherein the expandable frame comprises a foreshortening portion having a plurality of cells and wherein the skirt has an axial dimension less than two cell lengths. 24. The prosthesis of claim 22, wherein the generally cylindrical portion of the skirt is configured to contact the expandable frame along a first surface and tissue of the native mitral valve along a second surface to create an axial barrier to fluid flow exterior to the prosthesis when deployed within the native mitral valve. 25. The prosthesis of claim 22, wherein an inner diameter of the generally cylindrical portion of the skirt substantially corresponds in size to an outer diameter of the frame along which the generally cylindrical portion extends.